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Printed in Singapore. All rights reserved Journal compilation r 2009 The Acta Anaesthesiologica Scandinavica Foundation
Review Article
Background: Several studies have assessed the effect of a regimen whereas two studies found no difference and two
‘liberal’ vs. a ‘restrictive’ perioperative fluid regimen on studies found differences in the selected outcome para-
post-operative outcome. The literature was reviewed in meters.
order to provide recommendations regarding periopera- Conclusion: Liberal vs. restrictive fixed-volume regimens
tive fluid regimens. are not well defined in the literature regarding the defini-
Methods: A PubMed search identified randomized clinical tion, methodology and results, and lack the use of or
trials and cited studies, comparing two different fixed fluid information on evidence-based standardized periopera-
volumes on post-operative clinical outcome in major surgery. tive care-principles (fast-track surgery), thereby preclud-
Studies were assessed for the type of surgery, primary and ing evidence-based guidelines for procedure-specific
secondary outcome endpoints, the type and volume of admi- perioperative fixed-volume regimens. Optimization of
nistered fluid and the definition of the perioperative period. perioperative fluid management may include a combina-
Also, information regarding perioperative care and type of tion of fixed crystalloid administration to replace extra-
anaesthesia was assessed. vascular losses and avoiding fluid excess, together with
Results: In the seven randomized studies identified, the individualized goal-directed colloid administration to
range of the liberal intraoperative fluid regimen was from maintain a maximal stroke volume.
2750 to 5388 ml compared with 998 to 2740 ml for the
restrictive fluid regimen. The period for fluid therapy
and outcome endpoints were inconsistently defined and
Accepted for publication 24 April 2009
only two studies reported perioperative care principles
and discharge criteria. Three studies found an improved r 2009 The Authors
outcome (morbidity/hospital stay) with a restrictive fluid Journal compilation r 2009 The Acta Anaesthesiologica Scandinavica Foundation
843
M. Bundgaard-Nielsen et al.
844
Table 1
Perioperative methodology and result of fixed volume randomized trials.
Study and year Procedure/ ASA I/II/ Fast- Blinding Epi Epi Anaesthesia Outcome Result
pt (n) III/IV (%) track intraop post-op
Lobo8 2002 Hemi – No No No No – Gastric Low: " GI recovery
colectomy/20 emptying time # LOS: High 9 days, low 6 days
Nisanevich13 Major abdominal 22/52/26/0 Yes Assessor No Yes i.v.: thio/ Death and Low:
2005 surgery/142 fentanyl, vola: complications " GI recovery
iso/NO # complications, LOS (High 9
days, low 8 days).
! death
Holte14 2007 Arthroplasty/48 29/48/23/0 Yes Double Yes Yes Epi/spinal Perioperative High:
physiology and # vomiting
organ function " coagulation, pulmonary
function
! exercise capacity, pain,
nausea, appetite, well-being,
fatigue, ileus, post-op
hypoxaemia, LOS
Holte11 2007 Colonic 22/25/53/0 No Double Yes Yes i.v.: prop/ Physiological High:
surgery/32 remi recovery # pulmonary function,
vasoactive hormones, total
complications
! exercise capacity, ileus,
pain, well-being, thirst,
headache, dizzy/drowsiness,
fatigue, LOS
845
M. Bundgaard-Nielsen et al.
Intraoperative Postoperative
6000 6000
5000 5000
Volume (ml)
4000 4000
3000 3000
2000 2000
1000 1000
0 0
7 11
28
5 12
39
3
6 10
5 12
7 14
39
6 10
02 8
05 1
05 1
00
00
00
00
00
00
0
00
00
20
20
20
0
.2
.2
2
.2
.2
.2
2
.2
.2
l.
tru al.
al
Ka al.
vic al.
ta
a
al
al
al
al
al
al
et
Ka p et
et
e
et
et
et
et
et
et
et
et
bo
bo
lte
n
h
y
on
lte
y
tru
Ka
bo
vic
Lo
Lo
Ho
Ho
b
ds
ds
Ka
ac
ac
ne
ne
an
an
M
M
sa
sa
Br
Br
Ni
Ni
Fig. 1. Intraoperative and post-operative administered fluid volume in randomized trials comparing ‘high’ vs. ‘low’ fluid regimens. Black
bar, ‘high’ volume regimen; Grey bar, ‘low’ volume regimen. Post-operative period as defined in Table 2.
reported in one trial13 and a battery of physiologi- the exclusion criteria in the study by Brandstrup
cal recovery variables was utilized as secondary et al.9 In the study by Nisanevich et al.13 hepatect-
outcome variables in two studies.11,14 omy, age o18 years, pregnancy, coagulopathy, renal
or hepatic dysfunction and congestive heart failure
were the exclusion criteria.
Outcome result One study reported that epidural analgesia was
Studies with improved outcome following a restricted fluid not used perioperatively8 and one study used
regimen (Table 2). Three of seven studies found that epidural analgesia both intra- and post-operatively9
a restrictive fluid regimen improved outcome after and the last study only used epidural analgesia
major abdominal surgery, with two studies show- post-operatively.13 However, no information was
ing improved gastro-intestinal recovery and a re- provided with regard to the site (thoracic vs. lum-
duced LOS from 9 to 6 days8 and from 9 to 8 days, bar) or the dose/composition of the epidural regi-
respectively.13 Two studies also showed an overall men. Two studies were assessor blinded,9,13 and
reduced incidence of complications (Table 1).9,13 one study was not blinded.8 Updated perioperative
However, the two trials reporting LOS did not evidence-based care principles including pre-opera-
define any criteria for discharge.8,13 All three stu- tive information, optimized opioid-reduced epi-
dies reported use of crystalloid, of which one study dural and systemic analgesia, avoidance of bowel
used a balanced solution (Ringers lactate)13 and two preparation, early post-operative mobilization and
studies used saline and dextrose/glucose8,9 (Table oral nutrition,15–17 were not described in any of
2). Two studies reported additional use of colloid the three studies recommending a restrictive fluid
(HAES 6%, HES 200/0.5).9,13 One study did not regimen.8,9,13
provide ASA classes8 and one study included only
a small number of ASA III patients (2%).9 In the Studies with no difference in outcome (Table 2). Two
remaining study, ASA ranged from I to III (18%).13 studies in colonic surgery showed no difference
Patients with impaired renal function, congestive between the liberal and the restrictive fluid regi-
cardiac failure, hepatic disease, diabetes mellitus, men with outcome expressed as wound infection12
ascites, peritoneal metastasis, impaired mobility, or gastro-intestinal recovery and LOS (7.2 days).10
anaemia or those taking drugs affecting gastroin- Patients with fever, infection, susceptibility to ma-
testinal mobility were excluded in the study by lignant hyperthermia, congestive heart failure, use
Lobo et al.,8 whereas pregnancy, lactation, mental of diuretics, renal failure and a history of pulmon-
disorders, alcohol consumption 435 U/week, dia- ary oedema were excluded in the study by Kabon
betes mellitus, renal insufficiency, disseminated et al.12 For MacKay et al.10 renal impairment,
cancer, secondary cancer, inflammatory bowel dis- physical disability requiring long-term care, insu-
ease or disease hindering epidural analgesia were lin-dependent diabetes mellitus, total colectomy,
846
Table 2
Perioperative fluid administration and losses in millilitres.
Study Pre Intra Post
H L Definition All Cryst vol, Colloid vol, Blood Blood Diuresis Definition All Cryst Diuresis Weight gain
type type loss kg/24 h
H L H L H L H L H L H L H L H L H L H L
Lobo8 – – Intra 2800 2500 2800 2500 0 0 0 0 238 275 1190 776 To midnight 2900 600 2900 600 1190 1741 2.6 0.6
S1D S1D
Brandstrup9 500 0 To 5388 2740 – – – – – – 500 400 – – First post- 1500 500 – – – – 2.8 0.6
midnight op day
S1G S1G HAES HAES
Kabon12 700 0 Intra – – 3900 2500 – – – – 322 333 490 310 1 h post-op – – 1100 600 – – – –
– –
Nisanevich13 – – Intra 3878 1408 – – – – – – 440 400 – – 24 h 2012 2170 – – – – – –
RL RL HAES HAES
Mackay10 – – Day 2750 2000 2750 2000 – – – – – – – – Day 1 2600 2000 2600 2000 – – 1.1 0.5
of OP post-op
S1D S1D
14
Holte – – Intra 4250 1740 3275 815 500 500 0 0 0 0 – – – – – – – – – 2.1 0.6
RL RL HES
Holte11 – – Intra1 5050 1640 3900 1140 500 500 0 0 305 200 1150 700 – – – – – – – 2.0 0.2
PACU
RL RL HES
Pre, pre-operative; Intra, intraoperative; Post, post-operative; All, all administered volume; Cryst, crystalloid; Definition, definition of period; H, high volume group; L, low volume
group; Post-op, post-operative; OP, operation; PACU, post-anaesthetic care unit; –, no information; S1D, saline and dextrose; S1G, saline and glucose; RL, ringeŕs lactate; HES,
hydroxyl ethyl starch 130/0.4; HAES, hydroxyl ethyl starch 200/0.5.
‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy
847
M. Bundgaard-Nielsen et al.
abdominoperineal resection and low-anterior re- dated perioperative evidence-based care principles
section requiring a defunctioning stoma were the including pre-operative information, optimized
exclusion criteria. Both studies reported the use of opioids-reduced analgesia, avoidance of bowel
crystalloid but the type was only stated in one preparation, early post-operative mobilization
study (saline and dextrose).10 The use of colloid and oral nutrition.15–17 In both studies, well-de-
was not reported. Details regarding anaesthesia scribed epidural anaesthesia was used intra- and
were only provided in one of the studies,12 and post-operatively and the type of general anaesthe-
information on epidural analgesia was not given. sia was provided in the colonic surgery study.
Updated perioperative evidence-based care princi-
ples including pre-operative information, opti-
mized opioid-reduced analgesia, avoidance of Discussion
bowel preparation, early post-operative mobiliza- Inconsistent outcome results and study designs
tion and oral nutrition were not described in the have been reported with the use of a liberal vs. a
two studies without a difference in outcome. restrictive fluid regimen. These inconsistencies re-
late both to the amount of administered fluid
Studies with differences in outcome (Table 2). The two volume in the liberal vs. restrictive fluid regimens,
blinded studies regarding knee arthroplasty14 and indications for additional fluid, and to the defined
colonic surgery11 showed benefit from a restrictive intra- and post-operative period as well as infor-
or a liberal fluid regimen in different functional mation on perioperative care principles hindering
parameters. For both studies, age o50 years, direct comparison and interpretation. Accordingly,
weight 4110 kg, BMI440, inability to perform it is recommended to abandon the terms liberal and
the pre-operative test programme, ASA IV, insu- restrictive when referring to the size of a fixed-
lin-dependent diabetes mellitus, NYHA class IV or volume fluid regimen. Although changes in body
MIo3 month, FEV1o1 l, psychiatric disorder, al- weight were reported in most studies, a conven-
cohol consumption 45 U/day, glucocorticoid and tionally calculated fluid balance was only provided
anticoagulant therapy or inability to provide in- in two studies. Nevertheless, the studies suggest
formed consent were the exclusion criteria. In the that the perioperative crystalloid excess impairs the
colonic surgery study, additional exclusion criteria post-operative outcome.
were inflammatory bowel disease, and in the knee
arthroplasty study, a contraindication to tranexa-
mic acid/epidural catheter, chronic opioid treat- Study design
ment and morphine intolerance were also the Exclusion criteria were extensive in most trials. In
exclusion criteria for participation. The study in order to apply the study findings to daily clinical
knee arthroplasty found reduced vomiting, im- practice, we consider that the patients included
proved pulmonary function and enhanced coagu- need to be representative for the procedure-specific
lation with the liberal regimen, but no difference population. In this context, the study by Brandstrup
between groups in exercise capacity, pain, nausea, et al.9 only included a limited number of ASA III
appetite, well-being, fatigue, ileus, post-operative patients (ASA I/II/III: 47/51/2%) and did not
hypoxaemia or LOS (4 days).14 The study in colonic represent the general population undergoing color-
surgery found an improvement in pulmonary ectal resection. Nevertheless, the worse outcome
function and post-operative hypoxaemia and a demonstrated by this relatively ‘healthy’ popula-
reduced vasoactive hormonal response (aldoster- tion by a liberal fluid regimen leading to a weight
one, renin and AT-II concentration) on administer- gain suggests that fluid excess should be avoided.
ing a liberal fluid regimen. Although the total
number of complications was reduced (Po0.01),
the number of patients with complications was not Standardized evidence-based perioperative care
significantly reduced (P 5 0.08).11 In addition, ex- principles
ercise-capacity, pain, nausea, thirst, headache, The majority of identified studies, except for the two
dizzy/drowsiness, fatigue, ileus and LOS (‘high’: double-blinded studies,11,14 did not describe perio-
2.5 days; ‘low’: 3 days) were not different perative care principles and discharge criteria in
(P 5 0.52). Both studies used a balanced crystalloid detail. This is unfortunate because pre-operative
(Ringer’s lactate) and a colloid (HES 140/0.4). Also, information, optimized non-opioid analgesia, avoid-
both studies were double-blinded and with up- ance of bowel preparation, early post-operative mo-
848
‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy
bilization and oral nutrition improve post-operative saline should be avoided because they induce
outcome per se.15–17 Thus, the study in abdominal hyperchloraemic acidosis.18
surgery applying the ‘fast-track’ methodology had a
median hospital stay of 3 days in both groups11 in
contrast to the studies reporting a reduction in LOS Clinical and research strategies
from 9 to 6 days8 and 9 to 8 days13 with a ‘restricted’ Because differences in surgical trauma, pre-opera-
regimen. Consequently, perioperative care needs to tive hydration, anaesthetic technique, co-morbidity,
be defined and evidence-based care principles gender and age are likely to influence the fluid
should be adopted in order to evaluate the effect of needs, a fixed-volume regimen is unlikely to both
fluid management per se.4 The same applies to semi- prevent hypovolaemia and the risk of hypervolae-
ambulatory procedures where application of evi- mia for every patient (Fig. 2).19 Therefore, rather
dence-based perioperative care and a liberal fluid than using a fixed volume of crystalloids as the
regimen ( 3 l) improved the post-operative out- main strategy of perioperative volume handling, it
come in the context of exercise capacity, balance should be used as a background fluid regimen to
function, thirst, dizzy/drowsiness and the hormonal replace extra-vascular fluid losses and with a focus
stress response compared with a restricted regimen on avoiding undesirable fluid excess and maintain-
( 1 l), probably reflecting functional hypovolaemia ing bodyweight.9 A more rational strategy for
with the restricted regimen.7 perioperative fluid therapy could also include a
tailored individualized treatment optimizing the
intravascular volume by providing maximization
of cardiac stroke volume with colloid boluses, the
Outcome parameters so-called individualized ‘goal-directed therapy’
In elective surgery, perioperative death is a rare concept.20–22 This strategy has improved outcome
event and studies with death as an outcome vari- in 10 randomized trials20,23,24 and may, in contrast
able require large sample sizes. Only one study to the fixed-volume regimens, offer a definition of
used death as a primary outcome variable,13 while ‘normovolaemia’.20,25 Thus, rather than choosing
LOS has been widely used as a secondary outcome between a fixed-volume regimen and a goal-direc-
variable. The LOS depends on multiple factors and ted concept, an approach is to combine the two
when precise discharge criteria are not defined, strategies because they replace losses from the
interpretation of LOS remains elusive. Thus, the extra- and intravascular fluid compartments, re-
two studies using LOS as an outcome parameter spectively.
and advocating a restrictive fluid regimen did not
describe discharge criteria.8,13 A reduction in post-
operative surgical complications is a tempting Conclusion
evaluation of the benefit of one fluid regimen
It is of concern that the literature pertaining to a
over another, provided that the registered compli-
liberal vs. a restrictive fixed-volume regimen is
cation is related to fluid therapy. Thus, the role of
inconsistent regarding the definitions, methodol-
fluid management in urinary tract infections may
ogy and defined outcome parameters, and most
be questioned, when exact criteria for use and
studies are hampered by the lack of information on
removal of a urinary bladder catheter are not
evidence-based standardized perioperative care
provided.9 Therefore, in studies addressing the
principles (fast-track surgery). Therefore, evi-
role of fluid therapy, it would be of interest to
dence-based guidelines for optimal procedure-spe-
evaluate functional outcome variables with a
cific perioperative fixed-volume regimens cannot
known or at least theoretically assumed relation-
be formulated. Rational perioperative fluid man-
ship with the amount of fluid administration.4
agement may include a combination of fixed crys-
talloid administration to replace extra-vascular
losses and individualized goal-directed colloid ad-
Type of fluid ministration to maintain a maximal cardiac stroke
The relative role of the optimal administration of volume. Yet, we consider that such an approach
crystalloid vs. colloid ratio has not been resolved. needs to be examined in procedure-specific studies
However, there is evidence favouring balanced combined with evidence-based principles for peri-
solutions with an electrolyte concentration similar operative care (fast-track surgery) in order to de-
to that found in plasma and large volumes of e.g. fine optimal perioperative fluid management.26
849
M. Bundgaard-Nielsen et al.
morbidity
procedure
comorbidities
preop hydration
bowel preparation
anaesthesia / neuroaxial blockade
↑ risk of:
↑ risk of:
oedema
organ hypoperfusion ileus
SIRS PONV
sepsis pulm complications
multi organ failure cardiac demands
Fig. 2. Relationship between perioperative administered fluid volume and post-operative morbidity and factors influencing shift of the
curve (arrow). Boxes indicate the risk of complications associated with deviation from normovolaemia. Modified from Bellamy.19 SIRS,
systemic inflammatory response syndrome; PONV, post-operative nausea and vomiting.
Finally, we consider it important to evaluate the gastrointestinal function after elective colonic resection: a
role of fluid therapy in outcome in high-risk pa- randomised controlled trial. Lancet 2002; 359: 1812–8.
9. Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E,
tients, rather than excluding such patients in future Ording H, Lindorff-Larsen K, Rasmussen MS, Lanng C,
studies. Wallin L, Iversen LH, Gramkow CS, Okholm M, Blemmer
T, Svendsen PE, Rottensten HH, Thage B, Riis J, Jeppesen
IS, Teilum D, Christensen AM, Graungaard B, Pott F. Effects
of intravenous fluid restriction on postoperative complica-
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